RESUMEN
BACKGROUND AND AIM: To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. METHODS AND RESULTS: Low- (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. CONCLUSIONS: HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake.
Asunto(s)
Miocardio/ultraestructura , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/efectos adversos , Angiotensina II/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Ecocardiografía , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Potasio/sangre , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Ratas Wistar , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Sodio/sangre , Sodio/orinaRESUMEN
MiRNAs regulate cardiac development, hypertrophy, and angiogenesis, but their role in cardiac hypertrophy (CH) induced by aerobic training has not previously been studied. Aerobic training promotes physiological CH preserving cardiac function. This study assessed involvement of miRNAs-29 in CH of trained rats. Female Wistar rats (n=7/group) were randomized into three groups: sedentary (S), training 1 (T1), training 2 (T2). T1: swimming sessions of 60 min/5 days/wk/10 wk. T2: similar to T1 until 8th wk. On the 9th wk rats swam 2×/day, and on the 10th wk 3×/day. MiRNAs analysis was performed by miRNA microarray and confirmed by real-time PCR. We assessed: markers of training, CH by ratio of left ventricle (LV) weight/body wt and cardiomyocytes diameter, pathological markers of CH (ANF, skeletal α-actin, α/ß-MHC), collagen I and III (COLIAI and COLIIIAI) by real-time PCR, protein collagen by hydroxyproline (OH-proline) concentration, CF and CH by echocardiography. Training improved aerobic capacity and induced CH. MiRNAs-1, 133a, and 133b were downregulated as observed in pathological CH, however, without pathological markers. MiRNA-29c expression increased in T1 (52%) and T2 (123%), correlated with a decrease in COLIAI and COLIIIAI expression in T1 (27%, 38%) and T2 (33%, 48%), respectively. MiRNA-29c was inversely correlated to OH-proline concentration (r=0.61, P<0.05). The E/A ratio increased in T2, indicating improved LV compliance. Thus, these results show that aerobic training increase miR-29 expression and decreased collagen gene expression and concentration in the heart, which is relevant to the improved LV compliance and beneficial cardiac effects, associated with aerobic high performance training.
Asunto(s)
Ventrículos Cardíacos/metabolismo , MicroARNs/metabolismo , Condicionamiento Físico Animal , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/patología , Citrato (si)-Sintasa/metabolismo , Femenino , Marcadores Genéticos/fisiología , Ventrículos Cardíacos/patología , Hidroxiprolina/metabolismo , Miocitos Cardíacos/patología , Ratas , Ratas Wistar , Función Ventricular Izquierda/fisiologíaRESUMEN
The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3-5 month-old mice lacking alpha(2A-) and alpha(2C-)adrenoceptors (alpha(2A)/alpha(2C)ARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased alpha(2A)/alpha(2C)ARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.
Asunto(s)
Angiotensina II/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/prevención & control , Miocardio/metabolismo , Condicionamiento Físico Animal/fisiología , Receptores Adrenérgicos alfa 2/genética , Animales , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Corazón/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/fisiología , Masculino , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Genéticos , Receptores Adrenérgicos alfa 2/metabolismo , Sistema Renina-Angiotensina/fisiología , Sistema Nervioso Simpático/fisiopatología , Disfunción Ventricular/fisiopatologíaRESUMEN
The present investigation was undertaken to study the effect of beta-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (alpha(2A)/alpha(2C)ArKO). alpha(2A)/alpha(2C)ArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and alpha(2A)/alpha(2C)ArKO mice. At 5 months of age, all alpha(2A)/alpha(2C)ArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, alpha(2A)/ alpha(2C)ArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in alpha(2A)/alpha(2C)ArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while beta-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wild-type control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in alpha(2A)/alpha(2C)ArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise training and carvedilol suggest future studies associating both therapies.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Insuficiencia Cardíaca/terapia , Propanolaminas/uso terapéutico , Animales , Carvedilol , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Ratones Noqueados , Condicionamiento Físico Animal , Distribución Aleatoria , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
The present investigation was undertaken to study the effect of â-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (alpha2A/alpha2CArKO). alpha2A/alpha2CArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and alpha2A/alpha2CArKO mice. At 5 months of age, all alpha2A/alpha2CArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, alpha2A/ alpha2CArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in alpha2A/alpha2CArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while beta-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wild-type control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in alpha2A/alpha2CArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise...